Vanda Pharmaceuticals, Inc . v. United States Food and Drug Administration

United States Court of Appeals
FOR THE DISTRICT OF COLUMBIA CIRCUIT
Argued September 25, 2024 Decided December 17, 2024
No. 23-5200
VANDA P HARMACEUTICALS, INC .,
APPELLANT
v.
UNITED S TATES FOOD AND DRUG A DMINISTRATION , ET AL.,
APPELLEES
Appeal from the United States District Court
for the District of Columbia
(No. 1:22-cv-01432)
Paul W. Hughes argued the cause for appellant. With him
on the briefs were Andrew Lyons-Berg and Tyler L. Bishop.
Steven A. Myers, Attorney, U.S. Department of Justice,
argued the cause for appellees. On the brief were Brian M.
Boynton, Principal Deputy Assistant Attorney General, Daniel
Tenny and Anna M. Stapleton, Attorneys, Samuel Bagenstos,
General Counsel, U.S. Department of Health and Human
Services, and James Allred, Associate Chief Counsel, U.S.
Food and Drug Administration.
Before: KATSAS and C HILDS , Circuit Judges, and
EDWARDS , Senior Circuit Judge.

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Opinion of the Court filed by Senior Circuit Judge
EDWARDS .
EDWARDS , Senior Circuit Judge: Companies seeking to
market drugs in the United States must first obtain approval
from the Food and Drug Administration (“FDA”). 21 U.S.C.
§ 355(a). Seeking to expedite this process, Congress enacted a
“fast track” approval program, pursuant to which the FDA shall
“facilitate the development and expedite the review” of a new
drug if it “demonstrates the potential to address unmet medical
needs” for a serious disease or condition. 21 U.S.C.
§ 356(b)(1). The dispute in this case concerns a fast track
request filed by Vanda Pharmaceuticals, Inc. (“Vanda”) with
the FDA for tradipitant, an investigational new drug product
that Vanda is developing for the treatment of gastroparesis.
Vanda claims that the FDA’s denial of fast track designation
for tradipitant was contrary to law, and arbitrary and capricious
agency action.
Before Vanda’s fast track request was filed, the FDA had
placed its drug on a partial clinical hold, as authorized by 21
U.S.C. § 355(i)(3). The clinical hold prevents any long-term
clinical studies on Vanda’s drug until long-term animal studies
have been completed to assess its toxicological effects. When
the FDA later assessed Vanda’s eligibility for fast track, the
clinical hold was a significant factor that led the agency to deny
Vanda’s request. The FDA essentially determined that, without
long-term studies, Vanda could not “demonstrate” that its drug
had the “potential to address” the unmet need for long-term
treatment of gastroparesis.
Vanda challenges the FDA’s denial as arbitrary,
capricious, and contrary to law under the Administrative
Procedure Act (“APA”), 5 U.S.C. § 706(2)(A). It contends that
the FDA erred in considering the clinical hold as a factor,

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improperly defined the “unmet medical need” at issue to
constitute long-term treatment only, and adopted a view of the
fast track program that was at odds with agency practice.
The District Court granted summary judgment for the
FDA and Vanda sought review in this court. While this appeal
was pending, Vanda also filed a complete New Drug
Application (“NDA”) for its drug, which the FDA has since
denied in its current form. This complete filing, the FDA
argues, has mooted the question presented here. We disagree,
and affirm the District Court’s decision on the merits. The FDA
properly considered the drug’s development plan in assessing
whether it qualified for fast track, and its denial of Vanda’s fast
track application was neither contrary to law nor arbitrary and
capricious.
I. B ACKGROUND
A. Statutory and Regulatory Framework
Before a new drug may be marketed in the United States,
the FDA must first confirm that it is safe and effective. Food,
Drug and Cosmetic Act (“FDCA”), 21 U.S.C. § 355(d). The
FDA process generally takes approximately ten months.
Manufacturers seeking to better study their drugs before filing
a marketing application may submit an Investigational New
Drug Application (“IND”) to the FDA. Id. § 355(i)(1), 21
C.F.R. § 312.20(a). The IND allows manufacturers to run
clinical trials before obtaining marketing approval. However,
if the FDA finds that the drug in question “represents an
unreasonable risk to the safety” of test subjects, it may impose
a clinical hold on such studies. 21 U.S.C. § 355(i)(3)(B). A
clinical hold halts any further studies or trials until the
manufacturer cures the issues that give the FDA pause.

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Aiming to “hasten research of the safety and effectiveness
of drugs” in some cases, Congress has enacted several
programs to expedite the FDA’s review process. Abigail All.
for Better Access to Developmental Drugs v. von Eschenbach,
495 F.3d 695, 699, n.4 (D.C. Cir. 2007). One such program, for
instance, designates a drug as a “breakthrough therapy” if
“preliminary clinical evidence” indicates that the drug offers a
“substantial improvement over existing therapies.” 21 U.S.C.
§ 356(a)(1). Another expedited review pathway is “accelerated
approval,” which may be granted if the FDA determines that
the drug in question “has an effect” that is “reasonably likely
to predict clinical benefit” for a condition, considering its
“severity, rarity, or prevalence” and the “lack of alternative
treatments.” Id. § 356(c)(1).
At issue here is the specific expedited program known as
“fast track.” Enacted as part of the FDA Modernization Act of
1997, the fast track statute provides that the FDA “shall take
such actions as are appropriate to expedite the development and
review” of a drug that is intended “for the treatment of a serious
or life-threatening disease or condition” if the drug in question
“demonstrates the potential to address unmet medical needs for
such a disease or condition.” Id. § 356(b)(1), (b)(3).
A fast track designation offers two main benefits to a drug
manufacturer. First, the FDA will “facilitate the development”
of the drug, usually by providing feedback in ongoing
discussions with the manufacturer. Id. § 356(b)(1); FDA,
Guidance for Industry: Expedited Programs for Serious
Conditions – Drugs and Biologics, Joint Appendix (“J.A.”)
672. Second, fast track drugs are reviewed on an expedited
schedule, and are considered for expedited review programs.
These include the accelerated approval program under section
356(c) and “rolling review,” in which the FDA provides
feedback to the manufacturer on individual portions of the

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application so that the developer may make any revisions
before filing a complete NDA. 21 U.S.C. § 356(d)(1).
Applicants may request a fast track designation
“concurrently with, or at any time after” their IND submission.
Id. § 356(b)(2). In reviewing requests for fast track, the FDA
requires that manufacturers list their drug’s proposed
indication in the application. Where a drug may have more than
one indication, applicants may file multiple fast track requests
or list multiple indications in the same application.
B. Factual Background
In 2016, Vanda submitted an IND to begin studying its
drug tradipitant for the treatment of gastroparesis, a chronic
stomach condition with persistent symptoms that include
abdominal pain, vomiting, and nausea. Vanda reported that
preliminary studies on gastroparesis patients in a four-week
drug trial showed that tradipitant had a statistically significant
effect on one of the “core” symptoms of gastroparesis, nausea.
There are two kinds of gastroparesis: idiopathic and
diabetic. The FDA currently recognizes one approved drug for
diabetic gastroparesis, which is only indicated for short-term
use of up to three months due to risks of serious side effects
after 12 months of use. There are no FDA-approved drugs
specifically for idiopathic gastroparesis, although the treatment
of its symptoms – including nausea – is the same as for diabetic
gastroparesis.
Vanda’s relevant discussions with the FDA regarding
tradipitant began in April 2018, when it submitted a proposal
to extend its four-week clinical trial of the drug by 12 months.
The FDA denied this proposal, requiring a nine-month animal
study to assess the drug’s long-term toxicity before Vanda

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could proceed with long-term studies in humans. Vanda
refused to conduct such studies, citing its ethical opposition to
nonrodent testing that requires sacrificing the animal. As a
result of this refusal, the FDA imposed a partial clinical hold,
as authorized by 21 U.S.C. § 355(i)(3), which prevents further
long-term clinical studies until Vanda conducts the required
animal studies. While the hold is in place, Vanda can still
conduct short-term clinical studies. In a separate litigation,
Vanda sought judicial review of the clinical hold and the
District Court upheld the FDA’s order. Vanda Pharm., Inc. v.
FDA (“Vanda I”), 436 F. Supp. 3d 256 (D.D.C. 2020). Vanda
did not appeal this decision.
In March 2019, Vanda requested that tradipitant be
designated a “breakthrough therapy” for the treatment of
gastroparesis under 21 U.S.C. § 356(a). Pointing to issues with
the study’s conclusions and its findings of the drug’s
effectiveness on nausea symptoms, the FDA denied this
request. The FDA also advised Vanda that it was “considering
an indication for the short-term relief of nausea in
gastroparesis” and encouraged Vanda to “further evaluate
tradipitant for this use” in future submissions. Letter from FDA
Director Julie Beitz to Vanda Denying Appeal of Denial of
Breakthrough Therapy Designation for Tradipitant (Feb. 28,
2020) [hereinafter FDA Letter Affirming Breakthrough
Therapy Designation Denial], J.A. 657.
Finally, in 2021, Vanda filed the fast track application that
is the subject of this litigation. Rather than taking the FDA’s
recommendation to tailor its application to short-term relief,
Vanda once again framed tradipitant’s indication as for the
symptoms of gastroparesis broadly. As with its previous
applications, Vanda’s fast track request described the
symptoms of gastroparesis as “chronic” and “persistent,” with
most patients “requir[ing] long-term medications.” Vanda

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Pharma., Inc., Request for Fast Track Designation 8-11 (Sep.
28, 2021), J.A. 177-80.
The FDA denied Vanda’s fast track request. While it
conceded that gastroparesis is a serious condition with an
unmet medical need, the agency found that the partial clinical
hold prevented Vanda from demonstrating that its drug could
address that need. This was because, being unable to conduct
long-term studies, Vanda could not obtain the data necessary
to demonstrate the product’s potential for the indication as
described in its application – i.e., to treat the symptoms of
gastroparesis, which are chronic, rather than to provide short-
term symptomatic relief.
In a contemporaneous internal memorandum, the FDA
elaborated that the unmet medical need tradipitant purported to
address was the long-term treatment of nausea symptoms, but
that no data on the drug’s effectiveness for this indication could
be generated while the clinical hold was in place. The FDA
further observed that the approach to treating nausea in patients
was the same whether the gastroparesis was diabetic or
idiopathic. The FDA also noted issues with Vanda’s study’s
methodology, including the use of rescue medication, which
the FDA was concerned may have tainted the results of
Vanda’s study. These internal notes, although not originally
disclosed to Vanda, mirror feedback that Vanda had previously
received from the FDA in connection with its breakthrough
designation application.
The FDA’s memo also included an internal checklist that
the FDA uses to assess fast track applications. The checklist
contains six main items, including whether the condition is
serious/life-threatening, and whether the product’s
development program was designed to demonstrate an effect
on a serious aspect of the condition. For these two items – items

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1 and 2 – the FDA marked “yes” when assessing Vanda’s fast-
track application. But it marked “no” as to items 3 and 4, which
ask if the product development plan addresses an unmet
medical need and if the product shows potential to address an
unmet medical need. Also relevant is item 5, which asks
whether the data supporting the request comes from trials that
are on clinical hold. Here, the FDA marked “yes.” The
checklist then recommends that, for fast track approval, items
1 through 4 must be answered “yes,” and that, if item 5 is
marked “yes,” – i.e., if there is a clinical hold in place – the fast
track application may not be granted.
In the face of the fast track denial and of the partial clinical
hold, Vanda could then pursue one of two courses of action.
First, it could file a new fast track application, tailored to the
short-term treatment of gastroparesis symptoms, as the FDA
suggested it do. Alternatively, it could conduct the required
animal studies to lift the clinical hold and proceed with long-
term studies to treat gastroparesis broadly. Vanda chose to
pursue neither of these options, which have remained open in
the course of this litigation. Instead, it filed suit in federal court
challenging the fast track denial as arbitrary and capricious
under the APA. While the District Court’s decision on cross-
motions for summary judgment was pending, Vanda then
submitted a complete NDA, requesting marketing approval of
its drug – once again, indicated broadly to treat gastroparesis
symptoms. The District Court granted summary judgment in
favor of the FDA. This appeal followed.
After this appeal was filed, the FDA reviewed Vanda’s
NDA and issued a Complete Response Letter denying the
application in its current form, finding that Vanda does not
provide substantial evidence of effectiveness for tradipitant for
the treatment of either symptoms of gastroparesis more broadly
or nausea specifically.

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II. ANALYSIS
A. Standard of Review
This Court reviews appeals from summary judgments de
novo, applying the standards set forth in Federal Rule of Civil
Procedure 56(a). See, e.g., Celotex Corp v. Catrett, 477 U.S.
317, 322 (1986). Under Rule 56(a), summary judgment is
warranted if the movant shows that “there is no genuine dispute
as to any material fact and the movant is entitled to judgment
as a matter of law.”
When reviewing agency decisions under the APA, we set
aside agency actions if we determine that they are “arbitrary,
capricious, an abuse of discretion, or otherwise not in
accordance with law.” 5 U.S.C. § 706(2)(A). An agency “acts
arbitrarily or capriciously if it ‘has relied on factors which
Congress has not intended it to consider, entirely failed to
consider an important aspect of the problem, offered an
explanation for its decision that runs counter to the evidence
before the agency, or is so implausible that it could not be
ascribed to a difference in view or the product of agency
expertise.’” Am. Wildlands v. Kempthorne, 530 F.3d 991, 997-
98 (D.C. Cir. 2008) (quoting Motor Vehicle Mfrs. Ass’n v. State
Farm Mut. Auto. Ins. Co., 463 U.S. 29, 43 (1983)).
Where the question is whether the agency action was
consistent with statutory authorization, our task is to determine
whether the agency acted consistently with the “best reading”
of the statute. Loper Bright Enterprises v. Raimondo, 144 S.
Ct. 2244, 2263 (2024). This judicial inquiry includes a
determination as to whether the statute in question “delegates
discretionary authority” to the agency and whether the agency
“engaged in reasoned decisionmaking within [the] boundaries”

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of that statutory delegation. Id. (internal quotation marks and
citations omitted).
B. Finality and Mootness
As a threshold matter, it is not clear that the denial of fast
track review is a final action that is subject to judicial review.
See Bennett v. Spear, 520 U.S. 154, 177-78 (1997). This is
because normally “[a] preliminary, procedural, or intermediate
agency action or ruling” is only “subject to review on the
review of the final agency action.” Yaman v. U.S. Dep’t of
State, 634 F.3d 610, 613 (D.C. Cir. 2011) (per curiam) (quoting
5 U.S.C. § 704).
This final order rule codifies the understanding that
“[p]remature review squanders judicial resources,” and that
litigants are generally “best served by a system which prohibits
piecemeal appellate consideration of rulings that may fade into
insignificance by the time proceedings conclude.” CSX
Transp., Inc. v. Surface Transp. Bd., 774 F.3d 25, 31 (D.C. Cir.
2014) (internal quotation marks and citations omitted). Thus,
we normally “reserv[e] judicial review until the end of an
adjudication,” when a judgment has been rendered on the
merits of the matter before the agency – in this case, until the
final completed NDA is ultimately denied. Id.; see also Holistic
Candlers & Consumers Ass’n v. FDA, 664 F.3d 940, 943 (D.C.
Cir. 2012) (finding that FDA warning letters are not reviewable
final agency actions because they “neither mark the
consummation of the agency’s decisionmaking process nor
determine the appellants’ legal rights or obligations”).
Neither party contends that the FDA’s Complete
Response Letter denying the NDA in its current form is a final
agency action, as it “simply afford[s] [Vanda] the opportunity
to provide additional information before the agency makes a

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final decision on the application.” Nostrum Pharms., LLC v.
FDA, 35 F.4th 820, 825 (D.C. Cir. 2022) (holding that a
“complete response letter is an interim step in the FDA’s
consideration of an application” and, therefore, not a final
agency action under 21 U.S.C. § 355(h)). Indeed, the Complete
Response Letter is not at issue in this case.
It is thus unclear under applicable law whether the FDA’s
denial of fast track review of Vanda’s application, on its own,
is a final order. We leave this question for another day,
however, because the FDA does not claim the disputed action
taken on Vanda’s fast track request was not a final action
subject to judicial review. As finality is not jurisdictional under
the APA, we therefore need not decide this matter. See Marcum
v. Salazar, 694 F.3d 123, 128 (D.C. Cir. 2012). Rather than
challenge finality, the FDA alleges a different justiciability bar,
contending that the fast track issue should be dismissed as
moot. We disagree.
We are “obliged to address the issue” of mootness because
it “goes to the jurisdiction of this court.” Row 1 Inc. v. Becerra,
92 F.4th 1138, 1143 (D.C. Cir. 2024) (internal quotation marks
and citation omitted). A claim is moot when “the issues
presented are no longer ‘live’ or the parties lack a legally
cognizable interest in the outcome.” Already, LLC v. Nike, Inc.,
568 U.S. 85, 91 (2013) (quoting Murphy v. Hunt, 455 U.S. 478,
481 (1982) (per curiam)). Intervening events may moot a claim
if they “make it impossible to grant the prevailing party
effective relief.” Lemon v. Geren, 514 F.3d 1312, 1315 (D.C.
Cir. 2008) (internal quotation marks and citation omitted).
While the party invoking mootness “bears the initial burden of
proving that no live controversy exists,” N. Am. Butterfly Ass’n
v. Wolf, 977 F.3d 1244, 1258 (D.C. Cir. 2020) (internal
quotation marks and citation omitted), this court still has the
“independent obligation to ensure that appeals before us are not

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moot.” Planned Parenthood of Wis., Inc. v. Azar, 942 F.3d 512,
516 (D.C. Cir. 2019) (internal quotation marks and citation
omitted).
The FDA contends that the denial of fast track review is
not a live issue at this juncture because any benefits of fast track
are inapplicable once the complete NDA has been filed. But
fast track is not an “all or nothing” package: that Vanda cannot
at this stage benefit from all of the features of the fast track
program, such as rolling review, does not mean it has no
concrete interest in the program. Because Vanda can still
benefit from other advantages the program confers, including
expedited review and facilitation opportunities, it retains a
“legally cognizable interest” in the resolution of the question
before us here. Already, 568 U.S. at 91.
First, now that the FDA has denied Vanda’s NDA in its
current form, Vanda may continue to discuss how to move
forward with its application, and will benefit from facilitation
of the drug’s development in these negotiations. We see no
reason why a fast track designation would confer no relief in
this ongoing process, and why it would therefore be
“impossible for a court to grant any effectual relief” to Vanda
if we determine that it should prevail on the merits. Knox v.
Serv. Emps. Int’l Union, Loc. 1000, 567 U.S. 298, 307 (2012)
(internal quotation marks and citation omitted). Even if the
benefits of such facilitation discussions are marginal in the face
of the substantial feedback Vanda has already received, this
concrete interest, “however small,” means that the case is not
moot. Id.
Second, while the application is in continued revision, fast
track status would still confer the concrete benefit of expedited
“review of the application” under section 356(b). Should
Vanda prevail on the merits, it would thus obtain the

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“opportunity to pursue a benefit” of expedited review of its
application, which is a “constitutionally cognizable” interest.
CC Distribs., Inc. v. United States, 883 F.2d 146, 150 (D.C.
Cir. 1989).
The FDA argues that completed NDAs are only
reviewable in an expedited fashion under “priority review,” a
separate review program which assesses whether the drug in
question would provide a significant improvement in safety
and effectiveness. It points to the fact that in filing its NDA,
Vanda concurrently requested priority review of its application.
But the fact that a complete NDA may benefit from priority
review does not necessarily mean that it cannot also qualify for
fast track. In fact, fast track applications may be filed “any time
after” the IND is submitted. 21 U.S.C. § 356(b)(2). Nor are
these two expedited review pathways interchangeable because,
as the FDA acknowledges, an application meeting the criteria
for fast track would not necessarily qualify for priority review.
Thus, Vanda could still receive the benefit of expedited review
“of the application” if it meets the fast track statutory criteria,
which are different from those for priority review.
Finally, even if the fast track status were a moot issue, the
facts here involve an agency action “capable of repetition yet
evading review.” Del Monte Fresh Produce Co. v. United
States, 570 F.3d 316, 322 (D.C. Cir. 2009). This exception to
the mootness doctrine applies “where (1) the challenged action
is in its duration too short to be fully litigated prior to cessation
or expiration, and (2) there is a reasonable expectation that the
same complaining party will be subject to the same action
again.” Kingdomware Techs., Inc. v. United States, 579 U.S.
162, 170 (2016) (cleaned up).
Because fast track applications must be reviewed within
60 days, 21 U.S.C. § 356(b)(3), the challenged action here is

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“too short to be fully litigated prior to its cessation or
expiration.” Del Monte, 570 F.3d at 322 (noting that “agency
actions of less than two years’ duration cannot be ‘fully
litigated’ prior to cessation or expiration”). And because the
FDA has made it clear that it invites Vanda to submit a
modified application for tradipitant indicated for short-term
symptoms of gastroparesis, there is “a reasonable expectation
that” any subsequent fast track applications will be subject to
the same assessment process that Vanda alleges is improper
here. Id.
We therefore proceed to the merits of Vanda’s claim.
C. The FDA’s Denial of Vanda’s Fast Track Application
Was Not Contrary to Law
Vanda first argues that the text of section 356(b) prohibits
the FDA from considering a clinical hold or other elements of
the drug’s development program when assessing a fast track
application. We disagree.
There are some provisions in the FDCA that are relatively
clear in indicating how the FDA should designate certain
products. See, e.g., Genus Med. Techs. LLC v. FDA, 994 F.3d
631, 633 (D.C. Cir. 2021) (interpreting FDCA provisions for
designation of products as “drugs” or “devices” where the
statute defined each term and rejecting the FDA’s
interpretation as inconsistent with the relevant statutory
definitions). The same is not true with respect to the fast track
provision in the FDCA. Rather, the statute leaves it for the FDA
to determine whether a drug “demonstrates the potential to
address unmet medical needs,” 21 U.S.C. § 356(b)(1), (b)(3),
and it does not define these terms. The statute merely
encourages the FDA to “utilize innovative and flexible

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approaches to the assessment of products” that address “unmet
medical needs.” Id. § 356(e)(1).
Vanda contends that the FDA could not consider the
clinical hold because the statute’s text allows the FDA to only
consider the “drug,” not the drug’s development program. In
other words, Vanda argues that because the statutory language
requires the FDA to assess whether the drug demonstrates the
potential to address unmet medical needs, the FDA
impermissibly deviated from the statute when it considered the
drug’s development program, including whether a clinical hold
was in place. This is an untenable distinction.
The statute places the burden on an applicant to
“demonstrate” that its drug meets the fast track criteria. To
assess whether this standard is met, the FDA obviously must
consider how the application puts forth the drug’s capacity to
address the indicated need. In doing so, the FDA may consider
past studies that have been conducted and how future studies
may further offer evidence of the drug’s efficacy. See
Prohibition Juice Co. v. FDA, 45 F.4th 8, 26 (D.C. Cir. 2022)
(explaining that the FDA shall deny an application where the
statute “requires that applicants make a certain showing before
their products can be approved” and the “applicant[s] fail[] to
make that showing”). Vanda points to no statutory language to
the contrary. Moreover, the fast track provision requires the
FDA to assess not only whether the drug currently addresses
unmet needs, but whether it has the “potential” to address them.
This language mandates an inherently prospective analysis. See
Potential, OXFORD ENGLISH DICTIONARY (2d ed. 1989). The
drug’s development plan, including what past and future
studies may demonstrate about the potential of the drug, are
plainly relevant and permissible considerations.

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Vanda’s self-serving interpretation of the statute is both
under- and overinclusive. It would preclude the FDA from
considering a drug’s development plan at all, even where it
might be lenient to an applicant whose drug has yet to show
results and who can only demonstrate its potential through a
development plan that may in the future prove the drug’s
effectiveness. Simultaneously, Vanda would require that the
FDA grant fast track to all applications that show that the drug
might in the future serve an unmet need, even if current studies
do not show that it is effective and future studies cannot be
conducted. Such a construction of the statute would render
superfluous the FDA’s role in determining whether a drug
“demonstrates” the potential defined by the statute, as it would
make virtually all drugs intended for treating the qualifying
conditions eligible for fast track. See Donnelly v. FAA, 411
F.3d 267, 271 (D.C. Cir. 2005) (“We must strive to interpret a
statute to give meaning to every clause and word, and certainly
not to treat an entire subsection as mere surplusage.”).
The best reading of the statute indicates that, in enacting
the fast track, Congress intended to benefit drugs that are not
yet fully effective but that can demonstrate their potential
effectiveness in addressing an unmet medical need in the
future. Assessing the drug’s development plan, including
whether future studies may be conducted to demonstrate its
potential or cure current data issues, is perfectly consistent with
that goal. By considering all available evidence, the FDA thus
lives up to the statutory mandate that it “utilize innovative and
flexible approaches” to determine whether to grant fast track
status, especially where current data on the drug’s effectiveness
may be scarce at the time the FDA is evaluating it for fast track.
21 U.S.C. § 356(e)(1).
The FDA previously informed Vanda of numerous
concerns it had about its tradipitant study. In the face of such

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issues with existing data, the agency’s consideration of whether
future studies might cure those problems is entirely consistent
with the statute’s mandate. It was equally reasonable for the
FDA to conclude that Vanda’s decision not to conduct
additional studies required to lift the partial clinical hold meant
that Vanda would not cure those issues and, thus, could not
demonstrate tradipitant’s potential to address the unmet need
that Vanda’s application identified.
D. The FDA Did Not Act Arbitrarily and Capriciously in
Denying Vanda’s Fast Track Application
On the record before us, we also conclude that the FDA
did not act arbitrarily or capriciously in assessing Vanda’s fast
track application.
First, it was permissible for the FDA to assess tradipitant
as indicated for long-term symptoms of gastroparesis. The
record – including Vanda’s own filings with the FDA – makes
clear that gastroparesis is a chronic disease. Indeed, the fact that
Vanda had previously sought to extend its clinical trials to 12
months indicates that it was interested in tradipitant’s long-
term effects. And, even after the FDA advised Vanda that it
should tailor its future submissions more narrowly to short-
term symptoms, Vanda did not do so, continuing to list
tradipitant’s indication as for the treatment of symptoms of
gastroparesis broadly. The fact that Vanda chose not to follow
that recommendation does not place the burden on the FDA to
divine a more specific indication for the drug than what Vanda
described in its application.
Moreover, as Vanda itself acknowledged in its application,
there is already a FDA-approved short-term treatment for
gastroparesis. In light of this alternative treatment and of
Vanda’s own description of the condition it set out to treat, the

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FDA was reasonable in defining the unmet medical need as the
need for long-term treatment of gastroparesis symptoms. And,
because the clinical hold precludes Vanda from demonstrating
that its drug will be an improvement on the current treatment’s
toxic long-term side effects, it was also reasonable for the FDA
to conclude that tradipitant could not demonstrate that it had
the potential to meet that need.
Second, it was also reasonable for the FDA not to address
tradipitant’s indication to treat idiopathic gastroparesis
separately, because the version of the disease is irrelevant to
the drug’s effectiveness to treat chronic nausea symptoms.
Vanda contends that, because idiopathic gastroparesis in
particular has no FDA-approved treatment, the FDA should
have granted fast track to tradipitant for that narrower
indication. But the lack of any approved idiopathic
gastroparesis treatment does not mean that tradipitant
necessarily meets that need. In fact, the record shows that
tradipitant’s only statistically significant effects are on the
symptom of nausea, which manifests the same way in both
idiopathic and diabetic gastroparesis. The FDA’s concerns with
Vanda’s nausea findings and with the clinical hold’s
foreclosure of long-term studies apply just as compellingly to
an indication for idiopathic gastroparesis as they do for
gastroparesis generally.
Finally, Vanda argues that the FDA had already previously
indicated that tradipitant had “potential,” and had already
approved it for treatment in some circumstances, so the fast
track denial was an arbitrary contradiction of the agency’s prior
positions. This claim is without merit. An agency acts
unreasonably when it deviates from prior positions “in similar
situations,” which is plainly not the case here. Gen. Motors
Corp. v. Nat’l Highway Traffic Safety Admin., 898 F.2d 165,
174 (D.C. Cir. 1990).

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19
Vanda first points to a letter in which an FDA director,
while affirming the FDA’s denial of breakthrough therapy
designation under the separate standard governed by section
356(a), states that she saw “a potential therapeutic role for
tradipitant, particularly for the short-term relief of nausea in
gastroparesis patients.” FDA Letter Affirming Breakthrough
Therapy Designation Denial, J.A. 657. But this non-binding
statement assessed tradipitant’s merits under the separate
standard of section 356(a), and thus cannot indicate a shift in
agency position with regards to whether tradipitant met the
different criteria for fast track under section 356(b). See Gen.
Motors Corp., 898 F.2d at 174; Muwekma Ohlone Tribe v.
Salazar, 708 F.3d 209, 216 (D.C. Cir. 2013) (finding no
inconsistency where the agency’s positions did not involve
treating “similar situations differently”).
In any event, the FDA’s denial of both requests reflects a
consistent position, as the agency asserted many of the same
issues with the drug’s studies in both decisions. Immediately
after the language Vanda quotes, the FDA director observed
that “additional data would be needed” to support a
breakthrough therapy designation. FDA Letter Affirming
Breakthrough Therapy Designation Denial, J.A. 657. The
director also added that Vanda’s application was for a broader
indication than its data supported, as it was “for ‘the treatment
of gastroparesis’, not for the treatment of a single symptom
associated with gastroparesis.” Id. Instead, the agency advised
that Vanda “should not submit a request for Breakthrough
Therapy Designation to treat ‘gastroparesis’ based on a
treatment effect for nausea alone.” Id. The FDA’s denial of
Vanda’s fast track application is therefore consistent with its
prior feedback to Vanda, including that its current data did not
demonstrate the potential for tradipitant to treat gastroparesis
symptoms generally.

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20
Vanda’s second contention of a prior inconsistent agency
position is equally unpersuasive. Vanda refers to the FDA’s
prior approval of expanded access for tradipitant, which is not
only governed by a different statutory standard under 21 U.S.C.
§ 360bbb(b)(2), but is also wholly unrelated to expedited
approval. The expanded access program allows physicians,
subject to certain conditions, to request manufacturers to
provide an unapproved, investigational drug for the treatment
of specific patients, whom the physician in question will
monitor. Id. § 360bbb(b). Unlike breakthrough therapy,
accelerated approval, and fast track, expanded access does not
expedite a drug’s approval process. It merely authorizes its use
for certain patients in certain conditions if “the Secretary
determines that there is sufficient evidence of safety and
effectiveness to support the use of the investigational drug” in
the unique case of each petitioning patient. Id. § 360bbb(b)(2).
Vanda argues that because the FDA had already granted
expanded access for tradipitant to eight individuals, some of
whom have used the drug for over a year, tradipitant’s
“potential” under section 356(b) is met, and the FDA’s fast
track denial was therefore inconsistent with the expanded
access grant. But authorization for expanded access takes no
position on the drug’s marketing approval, likelihood of
success, or potential to treat patients on a broader scale. There
is no inconsistency between the FDA’s grant of expanded
access and its denial of fast track where these two programs
operate under different statutory standards and objectives.
Finally, Vanda’s ethical objections to the required animal
studies to lift the clinical hold, principled though they may be,
are beside the point. Having fully litigated the propriety of the
clinical hold in Vanda I, Vanda is estopped from raising any
new challenges to the hold that it could have raised earlier. See
Ashbourne v. Hansberry, 894 F.3d 298, 302 (D.C. Cir. 2018).

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21
Vanda attempts to circumvent res judicata by raising the novel
argument that the FDA Modernization Act 2.0, Pub. L. No.
117-328, enacted after Vanda I, now renders the clinical hold
unreasonable. But we do not reach this claim because Vanda
raises it for the first time on appeal, even though the relevant
statute was enacted before the District Court reached its
decision. See Zevallos v. Obama, 793 F.3d 106, 114 (D.C. Cir.
2015). Vanda is welcome to raise this argument before the
FDA as it continues to discuss tradipitant’s approval, as the
FDA is better positioned to assess the reasonableness of
scientific methodology than this court. See Smith v. Berryhill,
587 U.S. 471, 488 (2019) (“[A] federal court generally goes
astray if it decides a question that has been delegated to an
agency if that agency has not first had a chance to address the
question.”).
In light of the evidence before it, the FDA reasonably
interpreted Vanda’s fast track application as targeting the
chronic symptoms of gastroparesis, which necessarily requires
that tradipitant meet the unmet need for long-term treatment.
The FDA’s focus on the drug’s effects on chronic symptoms is
wholly consistent with the record and demonstrates a “rational
connection between the facts found and the choice made.” State
Farm, 463 U.S. at 43 (internal quotation marks and citation
omitted); see also Growth Energy v. EPA, 5 F.4th 1, 16 (D.C.
Cir. 2021) (per curiam) (“[B]ecause the agency examined the
relevant data and articulated a satisfactory explanation for its
action, we uphold its decision.” (internal quotation marks and
citation omitted)). We therefore find that the FDA’s denial of
Vanda’s fast track application was neither arbitrary nor
capricious.

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III. CONCLUSION
For the reasons set forth above, we affirm the District
Court’s grant of summary judgment to the FDA. Vanda
remains free to continue its negotiations with the agency,
including to file an amended application pursuing a short-term
indication for its drug, or to proceed to lift the partial clinical
hold.
So ordered.

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